Monoamine oxidase (MAO) is primarily responsible for the neuronal degradation of biogenic amines. This enzyme is expressed in all cells; two types of activity (A and B) can be distinguished by their substrate specificity and drug sensitivity. We will assess the number of gene loci involved in expression of enzyme activity and the genetic basis of differences between A and B types of activity. Cultured cells will be used including continuous lines of neuroblastoma, hepatoma and L-cells, as well as normal human fibroblasts. (3-H)Parglyine (an irreversible inhibitor) will be used to label the enzyme. Proteins will be analyzed using gel electrophoresis and autoradiography. We will determine the number of protein species associated with A and B types of activity and whether differences in electrophoretic mobility exist based on types of activity or species or origin. Selection techniques will be developed to obtain cells varying in expression of MAO activity. Cells with MAO activity will be selected by their ability to survive exposure to drugs whose toxicity is alleviated by deamination, cells without activity by the toxicity of aldehydes formed from MAO substrates. Established techniques of somatic cell hybridization will be used to map the chromosomal location of genes responsible for activity. We will also look for endogenous polymorphisms of MAO in the normal human population. Skin fibroblasts will be used which express both A and B types of activity. Activity from different individuals will be compared with respect to reaction velocity, substrate affinity, turnover number, heat sensitivity and electrophoretic mobility. These studies will provide insight into the molecular nature of MAO and inherited variations in enzyme activity.